1. Field of the Invention
The present invention relates to an in vivo antioxidant composition comprising enol form .delta.-lactone of diketogulonic acid (2,3,6-trihydroxy-4-oxo-2-hexen-5-olide) and/or its sodium salt, potassium salt or calcium salt and more particularly, to a composition for reducing the toxicity of Adriamycin using in combination with vitamin E which is a fat-soluble antioxidant, a composition for reducing radiation injury using in combination with vitamin E, a composition for reducing disturbance due to lipid peroxidation in liver using in combination with vitamin E, a composition for reducing a peroxidized state in vivo, for example, a peroxidized state in vivo in Alloxan-induced diabetes, and a composition for reducing a peroxidized state in vivo in a broad sense.
The present invention also relates to a method for reducing or improving a peroxidized state in vivo by administering the aforesaid drug composition to mammal or human.
2. Description of the Prior Art
Anti-tumor agents such as Adriamycin generate activated oxygen to cause peroxidation in myocardiac tissue, etc. Due to these severe side effects, it is difficult to sufficiently enhance their therapeutic coefficient.
Most of radiation injuries are caused by peroxidation based on the oxygen effect: liver poison such as an organic halogen compound, etc. generates radicals to cause lipid peroxidation in liver, and Alloxan generates activated oxygen to cause peroxidation of pancreas .beta. cells to lower the secretion of insulin (pancreas .beta. cells show a high xanthine oxidase activity but have a low superoxide dismutase activity and it is generally considered that pancreas .beta. cells would be one of cells most susceptible to peroxidation in vivo).
In order to reduce oxygen toxicity due to these peroxidation reactions, it has been attempted to use vitamin E, vitamin C, CoQ.sub.10, glutathione and the like. However, no satisfactory effect has been obtained yet.
An antioxidant is generally a reducing agent and reacts with activated oxygen or radicals to eliminate them and on the other hand, itself is oxidized.
The oxidation product is reproduced to the original reduction type antioxidant by enzymatic or non-enzymatic "settling" effect, within the limit of injury in tissue cells. Where injury of tissue cells due to peroxidation is severe, however, the reproducing function is not sufficiently exhibited but the oxidation products produced from the antioxidant and harmful oxidation decomposition products or radicals produced therefrom cause secondary injury. This is regarded as drawbacks of conventional antioxidants.
Oxygen is difficultly soluble in an aqueous solution but readily soluble in the oil and fat phase. Components most susceptible to peroxidation in tissue cells are higher unsaturated fatty acids in the oil and fat phase of membrane. Accordingly, fat-soluble vitamin E plays an important role as an antioxidant in vivo. However, an extremely low amount of vitamin E can be retained in tissue cells and an excess amount of the vitamin E is rather disadvantageous. A sufficient antioxidant activity is not exhibited by the use of vitamin E alone.
Therefore, there is a theory that it would be necessary to utilize a synergistic effect or complementary effect using vitamin C in combination; vitamin C is a water-soluble antioxidant which is usable in large quantities. However, this theory is still insufficient. Vitamin C is fallen into a dilemma that it accelerates peroxidation in such a state that iron ions, copper ions, etc. are liberated, namely, in such a state that the "settling" effect is not sufficiently exhibited.